Subscribe to RSS
DOI: 10.1055/s-2007-990304
© Georg Thieme Verlag KG Stuttgart · New York
Statistical Fluctuations in Attractor Networks Related to Schizophrenia
Publication History
Publication Date:
17 December 2007 (online)
Abstract
We present a hypothesis of how the positive, negative, and cognitive symptoms of schizophrenia could be related to alterations in the stability of cortical networks which lead to a reduced signal-to-noise ratio. We analyze using integrate-and-fire simulations of attractor networks how some of the symptoms of schizophrenia could be related to a reduced depth of basins of attraction, produced by for example a decrease in the NMDA receptor conductances, and to statistical fluctuations caused by stochastic spike firing of neurons. Both of these processes contribute to instability in short term memory, attentional, and semantic neuronal networks. The cognitive symptoms such as distractibility, working memory deficits or poor attention could be caused by this instability of attractor states in prefrontal cortical networks. Lower firing rates are also produced, and in the orbitofrontal and anterior cingulate cortex could account for the negative symptoms including a reduction of emotions. If the decrease in NMDA conductances, and the statistical fluctuations, are combined with a reduction of GABA conductances, this causes the network to switch between the attractor states, and to jump from spontaneous activity into one of the attractors. We relate this to the positive symptoms of schizophrenia including delusions, paranoia, and hallucinations, which may arise because the basins of attraction are shallow and there is instability in temporal lobe semantic memory networks, leading thoughts to move too freely round the attractor energy landscape.
References
-
1 Abeles M.
Corticonics . New York: Cambridge University Press 1991 - 2 Bender W, Albus M, Moller HJ, Tretter F. Towards systemic theories in biological psychiatry. Pharmacopsychiatry. 2006; 39 ((Suppl 1)) S4-S9
-
3 Braitenberg V, Schütz A.
Anatomy of the Cortex . Springer Verlag, Berlin 1991 - 4 Brunel N, Wang X. Effects of neuromodulation in a cortical network model of object working memory dominated by recurrent inhibition. Journal of Computational Neuroscience. 2001; 11 63-85
- 5 Capuano B, Crosby IT, Lloyd EJ. Schizophrenia: genesis, receptorology and current therapeutics. Curr Med Chem. 2002; 9 ((5)) 521-548
- 6 Carlsson A. The neurochemical circuitry of schizophrenia. Pharmacopsychiatry. 2006; 39 ((Suppl 1)) S10-S14
- 7 Castner SA, Williams GV, Goldman-Rakic PS. Reversal of antipsychotic-induced working memory deficits by short-term dopamine D1 receptor stimulation. Science. 2000; 287 ((5460)) 2020-2022
- 8 Cohen JD, Servan-Schreiber D. Context, cortex, and dopamine: a connectionist approach to behavior and biology in schizophrenia. Psychol Rev. 1992; 99 ((1)) 45-77
- 9 Coyle JT, Tsai G, Goff D. Converging evidence of NMDA receptor hypofunction in the pathophysiology of schizophrenia. Ann N Y Acad Sci. 2003; 1003 318-327
-
10 Dayan P, Abbott LF.
Theoretical Neuroscience . MIT Press, Cambridge, MA 2001 - 11 Deco G. A dynamical model of event-related fMRI signals in prefrontal cortex: predictions for schizophrenia. Pharmacopsychiatry. 2006; 39 ((Suppl 1)) S65-S67
- 12 Deco G, Rolls ET. Attention and working memory: a dynamical model of neuronal activity in the prefrontal cortex. European Journal of Neuroscience. 2003; 18 2374-2390
- 13 Deco G, Rolls ET. Attention, short term memory, and action selection: a unifying theory. Progress in Neurobiology. 2005; 76 236-256
- 14 Durstewitz D. A few important points about dopamine's role in neural network dynamics. Pharmacopsychiatry. 2006; 39 ((Suppl 1)) S72-S75
- 15 Durstewitz D, Seamans JK. The computational role of dopamine D1 receptors in working memory. Neural Netw. 2002; 15 ((4-6)) 561-572
- 16 Durstewitz D, Seamans JK, Sejnowski TJ. Neurocomputational models of working memory. Nat Neurosci. 2000; 3 ((Suppl 1)) 184-191
- 17 Goldman-Rakic P. Working memory dysfunction in schizophrenia. Journal of Neuropsychology and Clinical Neuroscience. 1994; 6 348-357
- 18 Goldman-Rakic PS. The physiological approach: functional architecture of working memory and disordered cognition in schizophrenia. Biol Psychiatry. 1999; 46 ((5)) 650-661
- 19 Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia?. Am J Psychiatry. 1996; 153 ((3)) 321-330
- 20 Hoffman RE. Attractor neural networks and psychotic disorders. Psychiatric Annals. 1992; 22 ((3)) 119-124
- 21 Hoffman RE, MacGlashan TH. Using a speech perception neural network computer simulation to contrast neuroanatomic versus neuromodulatory models of auditory hallucinations. Pharmacopsychiatry. 2006; 39 ((Suppl 1)) S54-S64
- 22 Hopfield JJ. Neural networks and physical systems with emergent collective computational abilities. Proc. Nat. Acad. Sci. USA. 1982; 79 2554-2558
- 23 Koch KW, Fuster JM. Unit activity in monkey parietal cortex related to haptic perception and temporary memory. Exp. Brain Res. 1989; 76 292-306
- 24 Lewis DA, Hashimoto T, Volk DW. Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci. 2005; 6 ((4)) 312-324
- 25 Liddle PF. The symptoms of chronic schizophrenia: a re-examination of the positive-negative dichotomy. British Journal of Psychiatry. 1987; 151 145-151
- 26 Loh M, Deco G. Cognitive flexibility and decision making in a model of conditional visuomotor associations. European Journal of Neuroscience. 2005; 22 ((11)) 2927-2936
- 27 Moller HJ. Antipsychotic and antidepressive effects of second generation antipsychotics: two different pharmacological mechanisms?. Eur Arch Psychiatry Clin Neurosci. 2005; 255 ((3)) 190-201
- 28 Mueser KT, MacGurk SR. Schizophrenia. Lancet. 2004; 363 ((9426)) 2063-2072
-
29 Rolls ET.
Emotion Explained . Oxford University Press, Oxford 2005 -
30 Rolls ET. The neurophysiology and functions of the orbitofrontal cortex. In: Zald DH, Rauch SL, editors,
The Orbitofrontal Cortex . Oxford University Press, Oxford 2006: 95-124 -
31 Rolls ET, Deco G.
Computational Neuroscience of Vision . Oxford University Press, Oxford 2002 -
32 Rolls ET, Treves A.
Neural Networks and Brain Function . Oxford University Press, Oxford 1998 - 33 Rosenblatt F. The perceptron: A probabillstic model for information storage and organization in the brain. Psychological Review. 1958; 65 386-408
- 34 Seamans JK, Gorelova N, Durstewitz D, Yang CR. Bidirectional dopamine modulation of GABAergic inhibition in prefrontal cortical pyramidal neurons. J Neurosci. 2001; 21 ((10)) 3628-3638
- 35 Seamans JK, Yang CR. The principal features and mechanisms of dopamine modulation in the prefrontal cortex. Prog Neurobiol. 2004; 74 ((1)) 1-58
- 36 Seeman P, Schwarz J, Chen JF, Szechtman H, Perreault M, MacKnight GS. et al . Psychosis pathways converge via D2 high dopamine receptors. Synapse. 2006; 60 ((4)) 319-346
- 37 Seeman P, Weinshenker D, Quirion R, Srivastava LK, Bhardwaj SK, Grandy DK. et al . Dopamine supersensitivity correlates with D2 High states, implying many paths to psychosis. Proc Natl Acad Sci USA. 2005; 102 ((9)) 3513-3518
- 38 Softky WR, Koch C. The highly irregular firing of cortical cells is inconsistent with temporal integration of random EPSPs. J Neurosci. 1993; 13 ((1)) 334-350
- 39 Stevens JR. An anatomy of schizophrenia?. Arch Gen Psychiatry. 1973; 29 ((2)) 177-189
- 40 Trantham-Davidson H, Neely LC, Lavin A, Seamans JK. Mechanisms underlying differential D1 versus D2 dopamine receptor regulation of inhibition in prefrontal cortex. J Neurosci. 2004; 24 ((47)) 10652-10659
- 41 Tretter F, Scherer J. Schizophrenia, neurobiology and the methodology of systemic modeling. Pharmacopsychiatry. 2006; 39 ((Suppl 1)) S26-S35
- 42 Wang XJ. Probabilistic decision making by slow reverberation in cortical circuits. Neuron. 2002; 36 ((5)) 955-968
- 43 Wang XJ. Synaptic reverberation underlying mnemonic persistent activity. Trends Neurosci. 2001; 24 ((8)) 455-463
- 44 Wilson F, Scalaidhe S, Goldman-Rakic P. Functional synergism between putative gamma-aminobutyrate-containing neurons and pyramidal neurons in prefrontal cortex. Proceedings of the National Academy of Science. 1994; 91 4009-4013
- 45 Winterer G, Coppola R, Goldberg TE, Egan MF, Jones DW, Sanchez CE. et al . Prefrontal broadband noise, working memory, and genetic risk for schizophrenia. Am J Psychiatry. 2004; 161 ((3)) 490-500
- 46 Winterer G, Egan MF, Kolachana BS, Goldberg TE, Coppola R, Weinberger DR. Prefrontal electrophysiologic “noise” and catechol-O-methyltransferase genotype in schizophrenia. Biological Psychiatry. 2006; 60 ((6)) 578-584
- 47 Winterer G, Musso F, Beckmann C, Mattay V, Egan MF, Jones DW. et al . Instability of prefrontal signal processing in schizophrenia. Am J Psychiatry. 2006; 163 ((11)) 1960-1968
- 48 Winterer G, Weinberger DR. Genes, dopamine and cortical signal-to-noise ratio in schizophrenia. Trends Neurosci. 2004; 27 ((11)) 683-690
- 49 Winterer G, Ziller M, Dorn H, Frick K, Mulert C, Wuebben Y. et al . Schizophrenia: reduced signal-to-noise ratio and impaired phase-locking during information processing. Clin Neurophysiol. 2000; 111 ((5)) 837-849
Correspondence
Dr. M. Loh
Universitat Pompeu Fabra
Computational Neuroscience
Passeig de Circumval.lació 8
08003 Barcelona
Spain
Phone: +34/93/542 23 62
Fax: +34/93/542 24 51
Email: marco.loh@upf.edu